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Pulmonary artery capacitance is a relatively novel measurement associated with adverse outcomes in pulmonary arterial hypertension. We sought to determine if preoperative indexed pulmonary artery capacitance was related to outcomes in paediatric heart transplant recipients, describe the changes in indexed pulmonary artery capacitance after transplantation, and compare its discriminatory ability to predict outcomes as compared to conventional predictors.
Methods:
This was a retrospective study of paediatric patients who underwent heart transplant at our centre from July 2014 to May 2022. Variables from preoperative and postoperative clinical, catheterisation, and echo evaluations were recorded. The primary composite outcome measure included postoperative mortality, postoperative length of stay in the top quartile, and/or evidence of end organ dysfunction.
Results:
Of the 23 patients included in the analysis, 11 met the composite outcome. There was no statistical difference between indexed pulmonary artery capacitance values in patients who met the composite outcome [1.8 ml/mmHg/m2 (interquartile 0.8, 2.4)] and those who did not [1.4 (interquartile 0.9, 1.7)], p = 0.17. There were no significant signs of post-operative right heart failure in either group. There was no significant difference between pre-transplant and post-transplant indexed pulmonary artery capacitance or indexed pulmonary vascular resistance.
Conclusions:
Preoperative pulmonary artery capacitance was not associated with our composite outcome in paediatric heart transplant recipients. It did not appear to be additive to pulmonary vascular resistance in paediatric heart transplant patients. Pulmonary vascular disease did not appear to drive outcomes in this group.
Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.
Auditory verbal hallucinations (AVHs) in schizophrenia have been suggested to arise from failure of corollary discharge mechanisms to correctly predict and suppress self-initiated inner speech. However, it is unclear whether such dysfunction is related to motor preparation of inner speech during which sensorimotor predictions are formed. The contingent negative variation (CNV) is a slow-going negative event-related potential that occurs prior to executing an action. A recent meta-analysis has revealed a large effect for CNV blunting in schizophrenia. Given that inner speech, similar to overt speech, has been shown to be preceded by a CNV, the present study tested the notion that AVHs are associated with inner speech-specific motor preparation deficits.
Objectives
The present study aimed to provide a useful framework for directly testing the long-held idea that AVHs may be related to inner speech-specific CNV blunting in patients with schizophrenia. This may hold promise for a reliable biomarker of AVHs.
Methods
Hallucinating (n=52) and non-hallucinating (n=45) patients with schizophrenia, along with matched healthy controls (n=42), participated in a novel electroencephalographic (EEG) paradigm. In the Active condition, they were asked to imagine a single phoneme at a cue moment while, precisely at the same time, being presented with an auditory probe. In the Passive condition, they were asked to passively listen to the auditory probes. The amplitude of the CNV preceding the production of inner speech was examined.
Results
Healthy controls showed a larger CNV amplitude (p = .002, d = .50) in the Active compared to the Passive condition, replicating previous results of a CNV preceding inner speech. However, both patient groups did not show a difference between the two conditions (p > .05). Importantly, a repeated measure ANOVA revealed a significant interaction effect (p = .007, ηp2 = .05). Follow-up contrasts showed that healthy controls exhibited a larger CNV amplitude in the Active condition than both the hallucinating (p = .013, d = .52) and non-hallucinating patients (p < .001, d = .88). No difference was found between the two patient groups (p = .320, d = .20).
Conclusions
The results indicated that motor preparation of inner speech in schizophrenia was disrupted. While the production of inner speech resulted in a larger CNV than passive listening in healthy controls, which was indicative of the involvement of motor planning, patients exhibited markedly blunted motor preparatory activity to inner speech. This may reflect dysfunction in the formation of corollary discharges. Interestingly, the deficits did not differ between hallucinating and non-hallucinating patients. Future work is needed to elucidate the specificity of inner speech-specific motor preparation deficits with AVHs. Overall, this study provides evidence in support of atypical inner speech monitoring in schizophrenia.
A series of chloro-alkylammonium montmorillonites was produced by cation exchange from Na+-montmorillonite. Gas chromatographic data were obtained for light hydrocarbons and certain oxides of nitrogen. Surface area and X-ray powder diffraction studies were made on each organo-clay, making possible differentiation between possible chromatographic pathways. Adsorption of the gas molecules on the silicate sheet was determined to be the dominant chromatographic pathway for all gases studied.
The UK Soft Drinks Industry Levy (SDIL) (announced in March 2016; implemented in April 2018) aims to incentivise reformulation of soft drinks to reduce added sugar levels. The SDIL has been applauded as a policy success, and it has survived calls from parliamentarians for it to be repealed. We aimed to explore parliamentary reaction to the SDIL following its announcement until two years post-implementation in order to understand how health policy can become established and resilient to opposition.
Design:
Searches of Hansard for parliamentary debate transcripts that discussed the SDIL retrieved 186 transcripts, with 160 included after screening. Five stages of Applied Thematic Analysis were conducted: familiarisation and creation of initial codebooks; independent second coding; codebook finalisation through team consensus; final coding of the dataset to the complete codebook; and theme finalisation through team consensus.
Setting:
The United Kingdom Parliament
Participants:
N/A
Results:
Between the announcement (16/03/2016) – royal assent (26/04/2017), two themes were identified 1: SDIL welcomed cross-party 2: SDIL a good start but not enough. Between royal assent – implementation (5/04/2018), one theme was identified 3: The SDIL worked – what next? The final theme identified from implementation until 16/03/2020 was 4: Moving on from the SDIL.
Conclusions:
After the announcement, the SDIL had cross-party support and was recognised to have encouraged reformulation prior to implementation. Lessons for governments indicate that the combination of cross-party support and a policy’s documented success in achieving its aim can help cement the resilience of it to opposition and threats of repeal.
Improving the quality and conduct of multi-center clinical trials is essential to the generation of generalizable knowledge about the safety and efficacy of healthcare treatments. Despite significant effort and expense, many clinical trials are unsuccessful. The National Center for Advancing Translational Science launched the Trial Innovation Network to address critical roadblocks in multi-center trials by leveraging existing infrastructure and developing operational innovations. We provide an overview of the roadblocks that led to opportunities for operational innovation, our work to develop, define, and map innovations across the network, and how we implemented and disseminated mature innovations.
New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or “hybrid” trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.
Patients with unbalanced common atrioventricular canal can be difficult to manage. Surgical planning often depends on pre-operative echocardiographic measurements. We aimed to determine the added utility of cardiac MRI in predicting successful biventricular repair in common atrioventricular canal.
Methods:
We conducted a retrospective cohort study of children with common atrioventricular canal who underwent MRI prior to repair. Associations between MRI and echocardiographic measures and surgical outcome were tested using logistic regression, and models were compared using area under the receiver operator characteristic curve.
Results:
We included 28 patients (median age at MRI: 5.2 months). The optimal MRI model included the novel end-diastolic volume index (using the ratio of left ventricular end-diastolic volume to total end-diastolic volume) and the left ventricle–right ventricle angle in diastole (area under the curve 0.83, p = 0.041). End-diastolic volume index ≤ 0.18 and left ventricle–right ventricle angle in diastole ≤ 72° yield a sensitivity of 83% and specificity of 81% for successful biventricular repair. The optimal multimodality model included the end-diastolic volume index and the echocardiographic atrioventricular valve index with an area under the curve of 0.87 (p = 0.026).
Conclusions:
Cardiac MRI can successfully predict successful biventricular repair in patients with unbalanced common atrioventricular canal utilising the end-diastolic volume index alone or in combination with the MRI left ventricle–right ventricle angle in diastole or the echocardiographic atrioventricular valve index. A prospective cardiac MRI study is warranted to better define the multimodality characteristic predictive of successful biventricular surgery.
Childhood adversities (CAs) predict heightened risks of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) among people exposed to adult traumatic events. Identifying which CAs put individuals at greatest risk for these adverse posttraumatic neuropsychiatric sequelae (APNS) is important for targeting prevention interventions.
Methods
Data came from n = 999 patients ages 18–75 presenting to 29 U.S. emergency departments after a motor vehicle collision (MVC) and followed for 3 months, the amount of time traditionally used to define chronic PTSD, in the Advancing Understanding of Recovery After Trauma (AURORA) study. Six CA types were self-reported at baseline: physical abuse, sexual abuse, emotional abuse, physical neglect, emotional neglect and bullying. Both dichotomous measures of ever experiencing each CA type and numeric measures of exposure frequency were included in the analysis. Risk ratios (RRs) of these CA measures as well as complex interactions among these measures were examined as predictors of APNS 3 months post-MVC. APNS was defined as meeting self-reported criteria for either PTSD based on the PTSD Checklist for DSM-5 and/or MDE based on the PROMIS Depression Short-Form 8b. We controlled for pre-MVC lifetime histories of PTSD and MDE. We also examined mediating effects through peritraumatic symptoms assessed in the emergency department and PTSD and MDE assessed in 2-week and 8-week follow-up surveys. Analyses were carried out with robust Poisson regression models.
Results
Most participants (90.9%) reported at least rarely having experienced some CA. Ever experiencing each CA other than emotional neglect was univariably associated with 3-month APNS (RRs = 1.31–1.60). Each CA frequency was also univariably associated with 3-month APNS (RRs = 1.65–2.45). In multivariable models, joint associations of CAs with 3-month APNS were additive, with frequency of emotional abuse (RR = 2.03; 95% CI = 1.43–2.87) and bullying (RR = 1.44; 95% CI = 0.99–2.10) being the strongest predictors. Control variable analyses found that these associations were largely explained by pre-MVC histories of PTSD and MDE.
Conclusions
Although individuals who experience frequent emotional abuse and bullying in childhood have a heightened risk of experiencing APNS after an adult MVC, these associations are largely mediated by prior histories of PTSD and MDE.
Using capture-recapture analysis we estimate the effective size of the active Amazon Mechanical Turk (MTurk) population that a typical laboratory can access to be about 7,300 workers. We also estimate that the time taken for half of the workers to leave the MTurk pool and be replaced is about 7 months. Each laboratory has its own population pool which overlaps, often extensively, with the hundreds of other laboratories using MTurk. Our estimate is based on a sample of 114,460 completed sessions from 33,408 unique participants and 689 sessions across seven laboratories in the US, Europe, and Australia from January 2012 to March 2015.
Admission laboratory screening for asymptomatic coronavirus disease 2019 (COVID-19) has been utilized to mitigate healthcare-associated severe acute respiratory coronavirus virus 2 (SARS-CoV-2) transmission. An understanding of the impact of such testing across a variety of patient populations is needed.
Methods:
SARS-CoV-2 nucleic acid amplification admission testing results for all asymptomatic patients across 4 distinct inpatient facilities between April 20, 2020, and June 14, 2021, were analyzed. Positivity rates and the number needed to test (NNT) to identify 1 asymptomatic infected patient were calculated. Admission results were compared to COVID-19 community incidence rates for the system’s surrounding metropolitan service area. Using a national survey of hospital epidemiologists, a clinically meaningful NNT of 1:100 was identified.
Results:
In total, 51,187 tests were collected (positivity rate, 1.8%). During periods of high transmission, the NNT met the clinically relevant threshold in all populations. The NNT approached or met the threshold for most locations during periods of lower transmission. For all transmission levels, the NNT for fully vaccinated patients did not meet the threshold.
Conclusions:
Implementing an asymptomatic patient admission testing program can provide clinically relevant data based on the NNT, even during periods of lower transmission and among different patient populations. Limiting admission testing to non–fully vaccinated patients during periods of lower transmission may be a strategy to address resource concerns around this practice. Although the impact of such testing on healthcare-associated COVID-19 among patients and healthcare workers could not be clearly determined, these data provide important information as facilities weigh the costs and benefits of such testing.
Evidence from developmental psychology on children's imagination is currently too limited to support Dubourg and Baumard's proposal and, in several respects, it is inconsistent with their proposal. Although children have impressive imaginative powers, we highlight the complexity of the developmental trajectory as well as the close connections between children's imagination and reality.
The Recruitment Innovation Center (RIC) has created a toolkit of novel strategies to engage potential participants in response to recruitment and retention challenges associated with COVID-19 studies. The toolkit contains pragmatic, generalizable resources to help research teams increase awareness of clinical trials and opportunities to participate; produce culturally sensitive and engaging recruitment materials; improve consent and return of results processes; and enhance recruitment of individuals from populations disproportionately impacted by COVID-19. This resource, the “RIC COVID-19 Recruitment and Retention Toolkit,” is available free online. We describe the toolkit and the community feedback used to author and curate this resource.
Gatherings where people are eating and drinking can increase the risk of getting and spreading SARS-CoV-2 among people who are not fully vaccinated; prevention strategies like wearing masks and physical distancing continue to be important for some groups. We conducted an online survey to characterise fall/winter 2020–2021 holiday gatherings, decisions to attend and prevention strategies employed during and before gatherings. We determined associations between practicing prevention strategies, demographics and COVID-19 experience. Among 502 respondents, one-third attended in person holiday gatherings; 73% wore masks and 84% practiced physical distancing, but less did so always (29% and 23%, respectively). Younger adults were 44% more likely to attend gatherings than adults ≥35 years. Younger adults (adjusted prevalence ratio (aPR) 1.53, 95% CI 1.19–1.97), persons who did not experience COVID-19 themselves or have relatives/close friends experience severe COVID-19 (aPR 1.56, 95% CI 1.18–2.07), and non-Hispanic White persons (aPR 1.57, 95% CI 1.13–2.18) were more likely to not always wear masks in public during the 2 weeks before gatherings. Public health messaging emphasizing consistent application of COVID-19 prevention strategies is important to slow the spread of COVID-19.
Advanced malignant neoplasms of the larynx and hypopharynx pose many therapeutic challenges. Total pharyngolaryngectomy and total laryngectomy provide an opportunity to cure these tumours but are associated with significant morbidity. Reconstruction of the pharyngeal defect following total pharyngolaryngectomy demands careful consideration and remains an area of debate within surgical discussions.
Methods
This paper describes a systemic analysis of pharyngeal reconstruction following total pharyngolaryngectomy and total laryngectomy, leveraging data collected over a 20-year period at a large tertiary referral centre.
Results
Analysing 155 patients, the results show that circumferential pharyngeal defects and prior radiotherapy have a significant impact on surgical complications. In addition, free tissue transfer in larger pharyngeal defects showed lower rates of post-operative anastomosis leak and stricture.
Conclusion
Pharyngeal resection carries a substantial risk of post-operative complications, and free tissue transfer appears to be an effective means of reconstruction for circumferential defects.
Clinical trials continue to face significant challenges in participant recruitment and retention. The Recruitment Innovation Center (RIC), part of the Trial Innovation Network (TIN), has been funded by the National Center for Advancing Translational Sciences of the National Institutes of Health to develop innovative strategies and technologies to enhance participant engagement in all stages of multicenter clinical trials. In collaboration with investigator teams and liaisons at Clinical and Translational Science Award institutions, the RIC is charged with the mission to design, field-test, and refine novel resources in the context of individual clinical trials. These innovations are disseminated via newsletters, publications, a virtual toolbox on the TIN website, and RIC-hosted collaboration webinars. The RIC has designed, implemented, and promised customized recruitment support for 173 studies across many diverse disease areas. This support has incorporated site feasibility assessments, community input sessions, recruitment materials recommendations, social media campaigns, and an array of study-specific suggestions. The RIC’s goal is to evaluate the efficacy of these resources and provide access to all investigating teams, so that more trials can be completed on time, within budget, with diverse participation, and with enough accrual to power statistical analyses and make substantive contributions to the advancement of healthcare.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
Iron and/or iodine deficiencies can have multiple serious adverse health outcomes, but examination of incidence rates of these deficiencies has rarely been conducted in any large population. This study examined incidence rates, temporal trends and demographic factors associated with medically diagnosed iron and iodine deficiencies/disorders in US military service members (SM).
Design:
The Defense Medical Epidemiological Database (DMED) was queried for medical visits of active duty SM to obtain specific International Classification of Diseases, Version 9, codes involving clinically diagnosed iron and iodine deficiencies/disorders.
Setting:
Analysis of existing database (DMED).
Participants:
Entire population of US military SM from 1997 to 2015 (average n per year = 1 382 266, 15 % women).
Results:
Overall incidence rates for iron and iodine were 104 and 36 cases/100 000 person-years, respectively. Over the 19-year period, rates for iron disorders increased steadily (108 % for men, 177 % for women). Rates for iodine disorders also increased steadily for men (91 %), but, for women, there was an initial rise followed by a later decline. Overall, women’s rates were 12 and 10 times higher than men’s for iron and iodine, respectively. Compared with whites, blacks and those of other races had higher rates of deficiencies of both minerals. Incidence rates for iodine deficiency increased substantially with age.
Conclusions:
The overall incidence of clinically diagnosed iron and iodine deficiency among SM was low, but increased over the 19 years examined, and certain demographic groups were at significantly greater risk. Given the unexpected increases in incidence of these mineral disorders, increased surveillance may be appropriate.